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Journal of Cachexia, Sarcopenia and... Jun 2024Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate... (Review)
Review
Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate endpoints. In cancer cachexia trials, the measurement of biomarkers features frequently. The aim of this systematic review was to assess the frequency and diversity of biomarker endpoints in cancer cachexia trials. A comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2023) was completed. Eligible trials met the following criteria: adults (≥18 years), prospective design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a biomarker(s) as an endpoint. Biomarkers were defined as any objective measure that was assayed from a body fluid, including scoring systems based on these assays. Routine haematology and biochemistry to monitor intervention toxicity were not considered. Data extraction was performed using Covidence, and reporting followed PRISMA guidance (PROSPERO: CRD42022276710). A total of 5975 studies were assessed, of which 52 trials (total participants = 6522) included biomarkers as endpoints. Most studies (n = 29, 55.7%) included a variety of cancer types. Pharmacological interventions (n = 27, 51.9%) were most evaluated, followed by nutritional interventions (n = 20, 38.4%). Ninety-nine different biomarkers were used across the trials, and of these, 96 were assayed from blood. Albumin (n = 29, 55.8%) was assessed most often, followed by C-reactive protein (n = 22, 42.3%), interleukin-6 (n = 16, 30.8%) and tumour necrosis factor-α (n = 14, 26.9%), the latter being the only biomarker that was used to guide sample size calculations. Biomarkers were explicitly listed as a primary outcome in six trials. In total, 12 biomarkers (12.1% of 99) were used in six trials or more. Insulin-like growth factor binding protein 3 (IGFBP-3) and insulin-like growth factor 1 (IGF-1) levels both increased significantly in all three trials in which they were both used. This corresponded with a primary outcome, lean body mass, and was related to the pharmacological mechanism. Biomarkers were predominately used as exploratory rather than primary endpoints. The most commonly used biomarker, albumin, was limited by its lack of responsiveness to nutritional intervention. For a biomarker to be responsive to change, it must be related to the mechanism of action of the intervention and/or the underlying cachexia process that is modified by the intervention, as seen with IGFBP-3, IGF-1 and anamorelin. To reach regulatory approval as an endpoint, the relationship between the biomarker and clinical benefit must be clarified.
Topics: Cachexia; Humans; Neoplasms; Biomarkers; Clinical Trials as Topic
PubMed: 38783477
DOI: 10.1002/jcsm.13491 -
PloS One 2024This study aimed to evaluate the intervention effect of curcumin on hepatic fibrosis in rodent models through systematic review and meta-analysis, in order to provide... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to evaluate the intervention effect of curcumin on hepatic fibrosis in rodent models through systematic review and meta-analysis, in order to provide meaningful guidance for clinical practice.
METHODS
A systematic retrieval of relevant studies on curcumin intervention in rats or mice hepatic fibrosis models was conducted, and the data were extracted. The outcome indicators included liver cell structure and function related indicators, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), ratio of albumin to globulin (A/G), total bilirubin (TBIL), bax protein, bcl-2 protein and index of liver, as well as the relevant indicators for evaluating the degree of hepatic fibrosis, such as hyaluronic acid (HA), laminin (LN), type I collagen (Collagen I), type III collagen (Collagen III), type III procollagen (PCIII), type III procollagen amino terminal peptide (PIIINP), type IV collagen (IV-C), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), α-Smooth muscle actin (α-SMA), hydroxyproline (HYP), platelet derived factor-BB (PDGF-BB), connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1), and oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px). These results were then analyzed by meta-analysis. Studies were evaluated for methodological quality using the syrcle's bias risk tool.
RESULTS
A total of 59 studies were included in the meta-analysis, and the results showed that curcumin can reduce the levels of ALT, AST, ALP, TBIL, bax protein, and index of liver in hepatic fibrosis models. It can also reduce HA, LN, Collagen I, Collagen III, PCIII, PIIINP, IV-C, TNF-α, α-SMA, HYP, PDGF-BB, CTGF, TGF-β1 and MDA, and increase the levels of ALB, A/G, SOD, and GSH-Px in the hepatic fibrosis models. However, the effects of curcumin on bcl-2 protein, IL-6 in hepatic fibrosis models and index of liver in mice were not statistically significant.
CONCLUSION
The analysis results indicate that curcumin can reduce liver cell apoptosis by maintaining the stability of liver cell membrane, inhibit the activation and proliferation of hepatic stellate cells by reducing inflammatory response, and alleviate tissue peroxidation damage by clearing oxygen free radicals.
Topics: Animals; Liver Cirrhosis; Curcumin; Mice; Rats; Disease Models, Animal; Oxidative Stress; Liver
PubMed: 38781262
DOI: 10.1371/journal.pone.0304176 -
Clinical Nutrition ESPEN Jun 2024Colorectal cancer (CRC) is the third most common malignancy in developed countries. Therefore, omega-3 fatty acids (O3FAs) have been suggested as a beneficial... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Colorectal cancer (CRC) is the third most common malignancy in developed countries. Therefore, omega-3 fatty acids (O3FAs) have been suggested as a beneficial complementary treatment due to their ability to regulate inflammatory responses and improve nutrition levels.This study aimed to evaluate the effects of O3FAs as a complementary treatment for inflammation, nutrition levels, post-operative infectious complications, and enhancement of recovery in CRC patients.
METHODS
The literature search was carried out through three databases. The outcomes of interest were assessed by measuring pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and CRP levels, serum albumin levels for nutrition assessment, post-operative infectious complications, and length of stay for recovery evaluation. Quality appraisal and meta-analysis were performed using RoB 2.0 and RevMan 5.4, respectively.
RESULTS
The result showed that O3FAs significantly reduced IL-6, CRP, and TNF-α, but did not affect IL-1β. Furthermore, the variable slightly increased serum albumin levels and the supplementation led to a decrease in post-operative infectious complications and shortened hospital stays.
CONCLUSION
O3FAs as a complementary treatment provided advantages for CRC patients, Further clinical trials and experiments should also be made emphasizing the impact and clinical implementation of O3FA in the nutritional status of CRC patients.
Topics: Humans; Fatty Acids, Omega-3; Colorectal Neoplasms; Nutritional Status; Dietary Supplements; C-Reactive Protein; Complementary Therapies; Inflammation; Postoperative Complications; Cytokines
PubMed: 38777451
DOI: 10.1016/j.clnesp.2024.04.002 -
Heliyon May 2024Influenza and COVID-19 patients share similar features and outcomes amongst adults. However, the difference between these diseases is not explored in paediatric age...
BACKGROUND
Influenza and COVID-19 patients share similar features and outcomes amongst adults. However, the difference between these diseases is not explored in paediatric age group especially in terms of inflammatory markers, coagulation profile and outcomes. Hence, we did this review to compare the inflammatory, coagulation features and outcomes between influenza and COVID-19 infected children.
METHODS
Literature search was done in PubMed Central, Scopus, EMBASE, CINAHL, Cochrane library, Google Scholar & ScienceDirect from November 2019 to May 2022. Risk of bias assessment was done through Newcastle Ottawa scale. Meta-analysis was done using random-effects model and the final pooled estimate was reported as pooled odds ratio (OR) or standardized mean difference (SMD) along with 95 % confidence interval (CI) depending on the type of outcome.
RESULTS
About 16 studies were included with most studies having higher risk of bias. Influenza paediatric patients had significantly higher erythrocyte sedimentation rate (ESR) (pooled SMD = 0.60; 95%CI: 0.30-0.91; I = 0 %), lactate dehydrogenase (LDH) (pooled SMD = 2.01; 95%CI: 0.37-3.66; I = 98.4 %) and prothrombin time (PT) (pooled SMD = 2.12; 95%CI: 0.44-3.80; I = 98.3 %) when compared to paediatric COVID-19 patients. There was no significant difference in terms of features like CRP, procalcitonin, serum albumin, aPTT, mortality and need for mechanical ventilation.
CONCLUSION
Inflammatory markers like ESR, LDH and PT was significantly higher in influenza patients when compared to COVID-19 in children, while rest of the markers and adverse clinical outcomes were similar between both the groups. Identification of these biomarkers has helped in understanding the distinctness of COVID-19 and influenza virus and develop better management strategies.
PubMed: 38765052
DOI: 10.1016/j.heliyon.2024.e30391 -
Clinical epidemiology and outcomes of emergency department-acute kidney injury: A systematic review.Heliyon May 2024Over half of all community-acquired acute kidney injury (CA-AKI) initially presented to emergency department (ED), but emergency department acute kidney injury (ED-AKI)...
BACKGROUND
Over half of all community-acquired acute kidney injury (CA-AKI) initially presented to emergency department (ED), but emergency department acute kidney injury (ED-AKI) is poorly characterised, poorly understood with no systematic review, often under-recognized and under-managed.
OBJECTIVE
To review the incidence, risk factors, and outcomes of ED-AKI, and risk factors of post-ED-AKI mortality globally.
METHODS
We included published prospective or retrospective observational studies, controlled trials, and systematic reviews reporting AKI in adult ED attendees within 24 h of ED admission. Iatrogenic causes of AKI from medical interventions were excluded. We used PubMed to identify articles from 1996 to August 14, 2021, and adopted the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies to assess risk of bias. We used a Forest plot to present pooled ED-AKI incidence rates and I statistics. Other parameters were summarized narratively.
RESULTS
Using 24 h from ED admission as the definition for ED-AKI we identified six articles from 2005 to 2018 in high-income settings and one article with a 48-h timeframe. The pooled incidence of ED-AKI was 20 per 1000 adult ED attendances. Risk factors for ED-AKI included increasing age, nursing home residence, previous hospital admission within 30 days, discharge diagnosis of diabetes, obstructive uropathy, sepsis, gastrointestinal medical conditions, high serum creatinine, bilirubin, C-reactive protein, white blood cell, alanine aminotransferase, low serum sodium or albumin on admission, poor premorbid renal function, antibiotic use, active malignancy, lung disease, hyperlipidaemia, and infection. Crude, all-cause 24-h mortality rate was 4.56 % and the one-year mortality rate was 35.04 %. Increasing age and comorbidities including cardiovascular disease and malignancy were associated with higher mortality rates.
CONCLUSION
The review reveals a paucity of relevant literature which calls for further research, increased vigilance, red flag identification, and standardized management protocols for ED-AKI.
PubMed: 38756601
DOI: 10.1016/j.heliyon.2024.e30580 -
Frontiers in Aging Neuroscience 2024Abnormal cerebrospinal fluid (CSF)/serum albumin ratio (Qalb) levels have been observed in patients with cognitive impairment. Few studies have specifically focused on... (Review)
Review
BACKGROUND
Abnormal cerebrospinal fluid (CSF)/serum albumin ratio (Qalb) levels have been observed in patients with cognitive impairment. Few studies have specifically focused on Lewy Body Disease (LBD), and the results were controversial. Thus, we conducted this systematic review and meta-analysis to investigate Qalb levels in patients with LBD by including data from different studies.
METHOD
We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases for a collection of studies containing studies comparing Qalb levels in patients with LBD and healthy controls (including healthy controls and other dementia subtypes). In the initial search, 86 relevant papers were retrieved. Standardized mean differences (SMD) in Qalb levels were calculated using a random effects model.
RESULTS
A total of 13 eligible studies were included. Mean Qalb levels were significantly higher in patients with LBD compared to healthy older adults [standardized mean difference (SMD): 2.95, 95% confidence interval (CI): 0.89-5.00, = 2.81, = 0.005]; and were significantly higher in patients with LBD than in patients with Alzheimer's disease (AD) (SMD: 1.13, 95% CI: 0.42-1.83, = 3.15, = 0.002);whereas mean Qalb levels were significantly higher in patients with frontotemporal lobar degeneration (FTLD) compared to those with AD (SMD: 1.13, 95% CI,0.14-2.13, = 2.24, = 0.03).
CONCLUSION
Qalb levels were significantly elevated in LBD patients compared with normal older adults and were higher than those in AD patients and FTLD patients, which helped in the differential diagnosis of LBD from other neurodegenerative diseases.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42024496616.
PubMed: 38756533
DOI: 10.3389/fnagi.2024.1390036 -
Liver Cancer Jun 2024Safety and outcome of atezolizumab/bevacizumab in Child-Pugh B patients with hepatocellular carcinoma (HCC) have not been completely characterized.
BACKGROUND
Safety and outcome of atezolizumab/bevacizumab in Child-Pugh B patients with hepatocellular carcinoma (HCC) have not been completely characterized.
OBJECTIVES
In this study, we aimed at addressing safety and efficacy of atezolizumab/bevacizumab in Child-Pugh B patients by reviewing the available data and analyzing them by meta-analysis.
METHODS
We compared the safety and efficacy of atezolizumab/becavizumab treatment in patients with unresectable HCC and various degrees of liver dysfunction. A total of 8 retrospective, non-randomized, cohort studies were included in this meta-analysis, for a total of 1,071 Child-Pugh A and 225 Child-Pugh B patients. The albumin-bilirubin (ALBI) grade was also used to assess liver function, when available.
RESULTS
Grade ≥3 adverse events were observed in 11.8% of Child-Pugh class A and 26.8% class B patients ( = 0.0001), with an odds ratio (OR) of 0.43 (confidence interval [CI] 0.21-0.90; = 0.02). Progression-free survival (PFS) at both 6 months (4.90 ± 2.08 vs. 4.75 ± 2.08 months; = 0.0004) and 12 months (8.83 ± 2.32 vs. 7.26 ± 2.33 months; = 0.002) was lower in Child-Pugh class B patients. A trend toward a higher objective response rate (ORR) was observed in Child-Pugh class A patients (219/856, 25.6%) as compared to Child-Pugh class B patients (25/138, 18.1%; = 0.070), while the probability of obtaining an ORR was significantly greater in Child-Pugh A patients (OR 1.79, CI 1.12-2.86; = 0.02). Median overall survival (OS) was 16.8 ± 2.0 and 6.8 ± 3.2 months in Child-Pugh A and B patients, respectively (mean difference 9.06 months, CI 7.01-11.1, < 0.0001). Lastly, OS was longer in patients with ALBI grades 1-2 than in those with grade 3 (8.3 ± 11.4 vs. 3.3 ± 5.0 months, = 0.0008).
CONCLUSIONS
Oncological efficacy of atezolizumab/bevacizumab is moderate in Child-Pugh class B patients, and the shorter PFS and OS associated with the greater likelihood of experiencing treatment-related adverse events observed in these patients suggest great caution and individualization of treatment, possibly with the support of the ALBI grade.
PubMed: 38756146
DOI: 10.1159/000533991 -
PloS One 2024The objective of this study was to evaluate the relationship between the platelet-to-lymphocyte ratio (PLR) and systemic lupus erythematosus (SLE). Additionally, the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this study was to evaluate the relationship between the platelet-to-lymphocyte ratio (PLR) and systemic lupus erythematosus (SLE). Additionally, the study aimed to establish an association between PLR and SLE disease activity, specifically lupus nephritis (LN).
METHODS
We conducted a comprehensive search across Medline, Embase, and Cochrane databases to identify relevant articles. Subsequently, we performed meta-analyses to compare PLR between SLE patients and controls, as well as active and inactive SLE cases, along with LN and non-LN groups. Furthermore, a meta-analysis was conducted on correlation coefficients between PLR and various parameters in SLE patients, including the SLE Disease Activity Index (SLEDAI), C3, C4, anti-dsDNA, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).
RESULTS
In total, fifteen studies comprising 1,522 SLE patients and 1,424 controls were eligible for inclusion. The meta-analysis demonstrated a significant elevation of PLR in the SLE group compared to the control group (Standardized Mean Difference [SMD] = 0.604, 95% Confidence Interval [CI] = 0.299-0.909, p < 0.001). Upon stratification by ethnicity, an elevated PLR was observed in the SLE group among both Asian and Arab populations. Subgroup analysis based on sample size revealed consistently higher PLR in both small (n < 200) and large sample (n ≥ 200) SLE groups. Moreover, when considering disease activity, there was a noteworthy trend of increased PLR in the active disease group compared to the inactive group (SMD = 0.553, 95% CI = 0.000-1.106, p = 0.050). However, the meta-analysis did not demonstrate a significant distinction in PLR between the LN and non-LN groups. Notably, a positive association was established between PLR and SLEDAI (correlation coefficient = 0.325, 95% CI = 0.176-0.459, p < 0.001). Furthermore, PLR exhibited positive correlations with ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels.
CONCLUSIONS
The outcomes of this meta-analysis underscored the elevated PLR in SLE patients, suggesting its potential as a biomarker for gauging systemic inflammation in SLE. Additionally, PLR exhibited correlations with SLEDAI, as well as with key indicators such as ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels.
Topics: Humans; Lupus Erythematosus, Systemic; Biomarkers; Lymphocytes; Blood Platelets; Inflammation; Blood Sedimentation; Platelet Count; C-Reactive Protein; Lupus Nephritis; Lymphocyte Count
PubMed: 38753735
DOI: 10.1371/journal.pone.0303665 -
Frontiers in Endocrinology 2024To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN).
METHODS
We conducted an umbrella review of existing meta-analyses of randomized controlled trials (RCTs) that focused on the effects of dietary intervention on DN incidence. The literature was searched via PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. According to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE), evidence of each outcome was evaluated and graded as "high", "moderate", "low" or "very low" quality to draw conclusions. Additionally, we classified evidence of outcomes into 4 categories.
RESULTS
We identified 36 meta-analyses of RCTs and 55 clinical outcomes of DN from 395 unique articles. Moderate-quality evidence suggested that probiotic supplementation could significantly improve blood urea nitrogen (BUN), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in DN patients. Low-quality evidence indicated that probiotic supplementation significantly improved the serum creatinine concentration, urinary albumin-creatinine ratio (UACR), fasting blood glucose (FBG), HbA1c and high-density lipoprotein cholesterol (HDL-C) in DN patients. In addition, low-quality evidence suggested that a salt restriction diet could significantly improve the creatinine clearance rate (CrCl) in patients with DN. Low-quality evidence suggested that vitamin D supplementation could significantly improve the UACR in patients with DN. In addition, low-quality evidence has indicated that soy isoflavone supplementation could significantly improve BUN, FBG, total cholesterol (TC), triglyceride (TG) and LDL-C levels in patients with DN. Furthermore, low-quality evidence suggested that coenzyme Q10 supplementation could significantly improve HbA1c, TC and HDL-C in patients with DN, and dietary polyphenols also significantly improved HbA1c in patients with DN. Finally, low-quality evidence suggested that supplementation with antioxidant vitamins could significantly improve the serum creatinine concentration, systolic blood pressure, and HbA1c level in patients with DN. Given the small sample size, all significantly associated outcomes were evaluated as class IV evidence.
CONCLUSION
Moderate to low amounts of evidence suggest that supplementation with probiotics, vitamin D, soy isoflavones, coenzyme Q10, dietary polyphenols, antioxidant vitamins, or salt-restricted diets may significantly improve clinical outcomes in patients with DN.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024512670.
Topics: Humans; Diabetic Nephropathies; Dietary Supplements; Meta-Analysis as Topic; Probiotics; Randomized Controlled Trials as Topic; Systematic Reviews as Topic
PubMed: 38742202
DOI: 10.3389/fendo.2024.1385872 -
Annals of Medicine Dec 2024It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of febuxostat in patients with hyperuricemia or gout by performing a meta-analysis of randomized controlled trials (RCTs).
METHODS
MEDLINE, Web of science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Randomized Controlled Trials were searched. The main outcomes included kidney events (serum creatinine doubling or progression to end-stage kidney disease or dialysis). The secondary outcomes were the rate of change in the estimated glomerular filtration rate (eGFR) and changes in the urine protein or urine albumin to creatinine ratio from baseline to the end of follow-up. We used random-effects models to calculate the pooled risk estimates and 95% CIs.
RESULTS
A total of 16 RCTs were included in the meta-analysis. In comparison with the control group, the patients who received febuxostat showed a reduced risk of kidney events (RR = 0.56, 95% CI 0.37-0.84, = 0.006) and a slower decline in eGFR (WMD = 0.90 mL/min/1.73 m, 95% CI 0.31-1.48, = 0.003). The pooled results also revealed that febuxostat use reduced the urine albumin to creatinine ratio (SMD = -0.21, 95% CI -0.41 to -0.01, = 0.042).
CONCLUSION
Febuxostat use is associated with a reduced risk of kidney events and a slow decline in eGFR. In addition, the urine albumin to creatinine ratio decreased in febuxostat users. Accordingly, it is an effective drug for delaying the progression of kidney function deterioration in patients with gout. PROSPERO CRD42021272591.
Topics: Humans; Creatinine; Disease Progression; Febuxostat; Glomerular Filtration Rate; Gout; Gout Suppressants; Hyperuricemia; Kidney; Kidney Failure, Chronic; Randomized Controlled Trials as Topic
PubMed: 38738384
DOI: 10.1080/07853890.2024.2332956